This application is in response to (PAR-02-058) Imaging - Science Track Award for Research Transition (I/START) for the study of neurobehavioral and neurobiological factors that may contribute to the initiation of substance use disorders (SUD). The first objective is to obtain preliminary fMRI measurements at 4T of individual functional differences in stimulant response coupled with objective behavioral measures of hyperactivity and structural MRI in a subgroup of male adolescents at risk for SUD, thus, replicating published findings at 1.5 T. The second is to develop preliminary data for an application targeting both male and female adolescents with conduct disorder (CD) under the auspices of a NIDA sponsored Mentored Research Scientist Development Award. Conduct disorder with behavioral hyperactivity (BH) and impulsivity is a known precursor to SUD, particularly with a positive family history of SUD. Behavioral hyperactivity, and its individual variation, is often cited as a critical link between CD and progression to SUD. We have measured, using optical tracking of movement, individual variations in BH, and have reported correlated blood flow abnormalities in dopamine transporter (DAT) rich subregions of the basal ganglia and cerebellum that were reduced, dose-dependently, by methylphenidate (MPH). Hyperactivity and stimulant response-rate appear to mirror disproportionate blood flow among DAT-rich subregions of the basal ganglia-cerebellar system. We hypothesize, those functional and/or structural defects in the basal ganglia-cerebellar system link BH with risk for SUD. To test functional and structural hypotheses about BH, responsiveness to MPH and volumes of DAT-rich subregions, we will examine, using phased-array MRI at 4T, four groups (n=10 each) of adolescent males (14-17 yrs). Two cohorts with (DSM-IV+) ADHD and comorbid oppositional defiant disorder ODD, having a first degree relative with SUD (SUD+), will be carefully screened with optical tracking for either presence (BH+/ SUD+) or absence of hyperactivity (BH-/SUD+) prior to scanning pro- and post-MPH, and compared with matched, (DSM-IV-) comparison groups, with (BH-/SUD+) and without (BH-/SUD-) a family history of SUD. Thus, imaging BH+/BH- individuals with ADHD/ODD will allow a prospective focus on antecedent neurobehavioral and neurobiological factors, in a population at high risk for SUD, without the confounds of developed CD or prior substance abuse on brain development.